基于自噬相关基因的头颈部鳞状细胞癌预后标志物的建立。
Development of a Prognostic Signature Based on Autophagy-related Genes for Head and Neck Squamous Cell Carcinoma.
机构信息
Department of General Dentistry, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, PR China.
Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, PR China; Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
出版信息
Arch Med Res. 2020 Nov;51(8):860-867. doi: 10.1016/j.arcmed.2020.09.009. Epub 2020 Sep 15.
BACKGROUND
Head and neck squamous cell carcinoma (HNSCC) is a malignant tumor with relative low survival rate. Increasingly evidences have emphasized the importance of autophagy in cancer initiation, progression, and the responses to cancer treatment.
AIM OF THE STUDY
This study aimed to investigate the potential biological and prognostic significance of autophagy-related genes (ARGs) in HNSCC patients.
METHODS
We collected a list of ARGs from Human Autophagy Database and obtained expression profiles and clinical information of HNSCC samples from the Cancer Genome Atlas (TCGA) portal. Differential expression analysis and functional enrichment analysis were performed by R software. The prognostic value of differentially expressed ARGs was detected by Cox regression analysis and prognosis-related ARGs were subjected to LASSO regression analysis. Univariate and multivariate Cox regression analysis were applied to identify promising independent prognosticators for HNSCC.
RESULTS
A total of 35 differentially expressed ARGs were screened out and functional enrichment analysis results indicated these genes were mainly associated with autophagy-related biological processes and pathways. Seven prognosis-related ARGs (ITGA3, CDKN2A, FADD, NKX2-3, BAK1, CXCR4, and HSPB8) were selected to construct a risk signature, which proved to be effective in predicting the survival rate of HNSCC patients. Moreover, univariate analysis showed risk score, tumor stage, T stage, and N stage were negatively correlated with patient overall survival and the multivariate Cox regression analysis results indicated risk score, age, and N stage was significantly associated with patient prognosis.
CONCLUSIONS
Our findings may provide novel evidences for the diagnosis and prognosis evaluation for HNSCC.
背景
头颈部鳞状细胞癌（HNSCC）是一种生存率相对较低的恶性肿瘤。越来越多的证据强调了自噬在癌症发生、进展和对癌症治疗的反应中的重要性。
目的
本研究旨在探讨自噬相关基因（ARGs）在 HNSCC 患者中的潜在生物学和预后意义。
方法
我们从人类自噬数据库中收集了一组 ARG 列表，并从癌症基因组图谱（TCGA）门户中获得了 HNSCC 样本的表达谱和临床信息。使用 R 软件进行差异表达分析和功能富集分析。通过 Cox 回归分析检测差异表达 ARG 的预后价值，并通过 LASSO 回归分析对预后相关 ARG 进行分析。应用单因素和多因素 Cox 回归分析鉴定 HNSCC 的有前途的独立预后因素。
结果
筛选出 35 个差异表达的 ARG，功能富集分析结果表明这些基因主要与自噬相关的生物学过程和途径相关。选择 7 个预后相关的 ARG（ITGA3、CDKN2A、FADD、NKX2-3、BAK1、CXCR4 和 HSPB8）构建风险特征，该特征被证明可有效预测 HNSCC 患者的生存率。此外，单因素分析显示风险评分、肿瘤分期、T 分期和 N 分期与患者总生存率呈负相关，多因素 Cox 回归分析结果表明风险评分、年龄和 N 分期与患者预后显著相关。
结论
我们的研究结果可能为 HNSCC 的诊断和预后评估提供新的依据。
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